MRFAP1L1

Chr 4

Morf4 family associated protein 1 like 1

Also known as: PP784

MRFAP1L1 enables identical protein binding activity, though its specific cellular function remains poorly characterized. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and seizures typically beginning in infancy. The gene shows relatively low constraint to loss-of-function variation, consistent with the recessive inheritance pattern observed in affected patients.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
86
P/LP submissions
0%
P/LP missense
1.73
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryMRFAP1L1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
86 unique Pathogenic / Likely Pathogenic· 24 VUS of 116 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.003
Z-score 0.31
OE 0.85 (0.411.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.41Z-score
OE missense 1.14 (0.951.36)
83 obs / 73.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.85 (0.411.73)
00.351.4
Missense OE1.14 (0.951.36)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 4 / 4.7Missense obs/exp: 83 / 73.1Syn Z: -0.88
DN
0.76top 25%
GOF
0.79top 10%
LOF
0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

116 submitted variants in ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic5
VUS24
Likely Benign2
81
Pathogenic
5
Likely Pathogenic
24
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
5
0
5
VUS
0
21
3
0
24
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total023890112

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MRFAP1L1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found